Low dose methotrexate is the cornerstone for the treatment of rheumatoid arthritis. One of its major drawbacks is hepatotoxicity, resulting in poor compliance of therapy. Dissatisfied arthritis patients are likely to seek the option of complementary and alternative medicine such as bee venom. The combination of natural products with modern medicine poses the possibility of potential interaction between the two groups and needs investigation. The present study was aimed to investigate the modulatory effect of bee venom acupuncture on efficacy, toxicity, and pharmacokinetics and tissue disposition of methotrexate. Complete Freund's adjuvant induced arthritic rats were treated for 3 weeks with methotrexate and/or bee venom. Arthritic score, ankle diameter, paw volume and tissue expression of NF-κB and TNF-α were determined to assess anti-arthritic effects, while anti-nociceptive effects were assessed by gait score and thermal hyperalgesia. Methotrexate toxicity was assessed by measuring serum TNF-α, liver enzymes and expression of NF-κB in liver. Combination therapy of bee venom with methotrexate significantly improved arthritic parameters and analgesic effect as compared to methotrexate alone. Bee venom ameliorated serum TNF-α and liver enzymes elevations as well as over expression of NF-κB in liver induced by methotrexate. Histological examination supported the results. And for the first time bee venom acupuncture was approved to increase methotrexate bioavailability with a significant decrease in its elimination. Conclusion: bee venom potentiates the anti-arthritic effects of methotrexate, possibly by increasing its bioavailability. Also, it provides a potent anti-nociceptive effect. Furthermore, bee venom protects against methotrexate induced hepatotoxicity mostly due to its inhibitory effect on TNF-α and NF-κB.

No abstract

Objective To evaluate the utility of gene therapy for uterine fibroids in the Eker rat model using an adenovirus-mediated delivery of a dominant negative estrogen receptor gene (Ad-DN-ER). Design Animal study. Setting University animal laboratory. Animal(s) 27 female Eker rats Interventions We randomized Eker rats with MRI-confirmed uterine leiomyomas to a single treatment of direct intra-fibroid injection with Ad-DN-ER, Ad-LacZ, or vehicle. Main Outcome Measures The tumor volumes determined by MRI scanning and caliber measurement. Samples of serum, fibroid tumors, and various organs were collected at 8, 15 30 days post-treatment to assess treatment safety and efficacy. Results Ad-DN-ER treatment significantly decreased uterine fibroid volume by 45%, 80% and 77.4% of pretreatment volume at days 8, 15 and 30 respectively and modulated the expression of apoptosis-, proliferation- and extracellular matrix related genes' when compared to control animals. Ad-DNER did not produce any toxic effects to non-target tissues. Conclusion Ad-DN-ER treatment shrinks Eker rats' fibroids, in part, via modulation of several estrogen regulated genes. This safe gene therapy approach presents a promising conservative treatment option for women with symptomatic uterine fibroids.

Benzo[alpha]pyrene (BaP) is one of the polycyclic aromatic hydrocarbons, which has shown carcinogenic, teratogenic, and mutagenic potentials. The reproductive toxicity of BaP in male was not well investigated. Thereby, we have addressed in the current study the testicular toxicity of BaP and the postulate whether or not the citrus flavonoid, hesperidin (HDN), could ameliorate such toxicity in male Swiss albino rats. In this sense, animals were challenged with BaP (50 mg/kg/day, orally) for 10 consecutive days. HDN (200 mg/kg/day, orally) was administered ahead of BaP challenge for 10 consecutive days. BaP induced testicular toxicity that was well characterized histologically and biochemically. It decreased the relative testis weight and induced pyknosis and necrobiotic changes as well as chromatolysis in the nuclei of the spermatocytes in the seminiferous tubules. It also markedly deteriorated epididymal function as shown by decreased sperm count, motility, and daily sperm production. The polyaromatic hydrocarbon also reduced the testicular activities of lactate dehydrogenase (LDH-X), superoxide dismutase (SOD), and glutathione-S-transferase (GST). Besides, it decreased the testicular reduced glutathione (GSH) but increased malondialdehyde (MDA) contents. Prior administration of HDN ahead of BaP challenge ameliorated all the histological and biochemical alterations induced by BaP. It improved the epididymal function and mitigated the injurious effects of BaP on the seminiferous tubules. In conclusion, HDN has proven protective effects in BaP-induced testicular toxicity paradigm, and this protection resides, at least in part, on its antioxidant properties.

Abstract:The possible uroprotective effects of curcumin have been addressed in the current study. Haemorrhagic cystitis was induced by challenging male Swiss albino rats with a single dose of cyclophosphamide (150 mg/kg, i.p.). Curcumin (200 mg/kg, i.p.) was administered for 10 consecutive days followed by a single dose of cyclophosphamide. Haemorrhagic cystitis was well characterized morphologically and biochemically. The hallmark of this toxicity was marked congestion, oedema and extravasation in rat urinary bladder, as well as a marked desquamative damage to the urothelium and severe inflammation in the lamina propria. Leucocytic infiltration was also observed and determined by histopathological examination. Serum level of tumour necrosis factor-alpha was notably elevated associated with apparent hypokalaemia and hyponatraemia. Bladder contents of adenosine triphosphate, reduced glutathione and glutathione-S -transferase activity were markedly reduced. Malondialdehyde level, myeloperoxidase activity and urinary nitrite-nitrate levels, expressed as nitric oxide, were dramatically increased. Prior administration of curcumin ahead of cyclophosphamide challenge improved all the biochemical and histologic alterations induced by the cytotoxic drug. Based on these broad findings, it could be concluded that curcumin has proven uroprotective efficacy in this cyclophosphamide haemorrhagic cystitis model, possibly through modulating the release of inflammatory endocoids, namely tumour necrosis factor-alpha and nitric oxide, improving the energy status and restoring the oxidant/antioxidant balance.